Ammonium Chloride → 1-Tert-butoxycarbonyl-4-[2-(4-methylphenylsulfanyl)phenyl]piperidin-4-ol

HRID 445007Notes

Reaction equation

HRID 445007 reaction equation
[Li]CCCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[S:13][C:14]1[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=1.[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].[NH4+].[Cl-]>C1COCC1>[C:21]([O:25][C:26]([N:28]1[CH2:33][CH2:32][C:31]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[S:13][C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)([OH:34])[CH2:30][CH2:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 21864904(2-Bromophenyl)(p-tolyl)sulfaneHCID 178418339Butyllithium

Product 1

HCID 218649151-Tert-butoxycarbonyl-4-[2-(4-methylphenylsulfanyl)phenyl]piperidin-4-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of BuLi (2.5 M in hexane, 12.0 ml, 30 mmol) was slowly added to a stirred solution of 1-bromo-2-(4-methylphenylsulfanyl)benzene (30 mmol) in dry THF (75 ml) under Argon at −78° C. The solution was stirred for 10 min before 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5.98 g, 30 mmol) was added in one portion. The solution was allowed to warm up to room temperature and then stirred for 3 h. Saturated aqueous NH4Cl (150 ml) was added and the solution was extracted with ethylacetate (150 ml). The organic phase was washed with brine, dried (MgSO4) and the solvent was evaporated in vacuo. Crude 1 was purified by flash chromatography on silica gel (eluent: Ethylacetat/heptane 20:80) to produce the target compound as a white foam. LC/MS (m/z) 399.3 (MH+); RT=3.82; purity (UV, ELSD): 98%, 100%; yield: 5.02 g (42%).

Workup

  1. additionwas added in one portion
  2. extractionthe solution was extracted with ethylacetate (150 ml)
  3. washThe organic phase was washed with brine
  4. dry with materialdried (MgSO4)
  5. customthe solvent was evaporated in vacuo
  6. customCrude 1 was purified by flash chromatography on silica gel (eluent: Ethylacetat/heptane 20:80)

Sources & evidence

ORD record
ord-d979a1e4f5d14127844e0a989813f626
Source dataset
uspto-grants-2013_07
Patent number
US08476279B2

Reaction notes

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